The
combination of high-throughput screening and synthetic chemistry provides an unprecedented opportunity for NIH-funded investigators to engage in discovery and
development of small molecule probes of biological pathways.

These probes could provide the tools needed to directly test whether drug-like molecules
can be developed that interact with a novel target of interest and have the effects that were predicted in studies using molecular and genetic approaches. Such
advances could provide a major step in the discovery of novel therapeutic agents by identifying the most viable approaches for further investment in an industry
setting.

In addition, academic investigators are increasingly engaged in tackling other critical issues inherent in modern drug discovery paradigms,
such as, how do we predict at an earlier stage whether a drug will have clinical efficacy of toxicity? Rather than gaining answers to these questions at the end
of a billion-dollar program, basic and clinical scientists can contribute to the design and execution of early proof-of-concept clinical studies that predict
ultimate efficacy, and which may lead to the development of biomarkers that predict later toxicity.

Multiple changes in science, business and society
are forcing a fundamental shift in traditional approaches to drug discovery. Realizing the exciting promise of recent advances in the face of fiscal constraints
presents a challenging but exciting opportunity.

Individuals across the spectrum of biomedical research and discovery share a common optimism that we
are at the beginning of the most exciting era yet in changing the face of human disease. It is critical, however, that different players in this arena find new
models to leverage our collective resources and talents.

This issue of Lens highlights one approach for bridging the gap to new
therapeutics.